Opioid use among pregnant women is increasing significantly, and consequently, a more than 5-fold increase in the incidence of neonatal abstinence syndrome (NAS) has been reported since 2000. Preliminary studies show that prenatal opioid exposure is associated with increased risk of impaired neurodevelopment across cognitive, motor and behavioral domains. Therefore, studies to rigorously characterize the impacts of prenatal opioid exposure on early brain development are critically needed. In our application, five institutions (Duke University, Arkansas Children?s Research Institute, Cincinnati Children?s Hospital, University of Illinois at Urbana-Champaign and University of North Carolina at Chapel Hill) with complementary expertise, have formed a consortium to develop strategies to prepare for the Phase II HEALthy Brain and Child Development Study, a planned large scale multi-site research study to examine the long-term impact of prenatal drug exposure on long term childhood outcomes. Leveraging the unique skills of our multidisciplinary team, we will develop essential instruments and strategies (recruitment/retention protocols, assessment batteries, and novel tools) for the Phase II study (Aim 1). We will conduct pilot studies (fetal and postnatal imaging, advanced imaging harmonization and quality control, assessment administration, biosampling) to evaluate instruments for the Phase II study (Aim 2). Finally, we will analyze available data (Aim 3), including imaging, behavioral, cognitive and maternal data from studies focusing on early brain development, to provide critical information to guide the Phase II study design. Upon completion of the proposed aims, our consortium will be in an ideal position to conduct the future Phase II study.